Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-31466
Alvino, E; Marra, G; Pagani, E; Falcinelli, S; Pepponi, R; Perrera, C; Haider, R; Castiglia, D; Ferranti, G; Bonmassar, E; Jiricny, J; Zambruno, G; D'Atri, S (2002). High-frequency microsatellite instability is associated with defective DNA mismatch repair in human melanoma. Journal of Investigative Dermatology, 118(1):79-86.
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Hereditary nonpolyposis colorectal cancers and a steadily increasing number of sporadic tumors display microsatellite instability. In colorectal tumors, high-frequency microsatellite instability is strictly associated with inactivation of the DNA mismatch repair genes hMSH2, hMLH1, or hPMS2, whereas mutations in the mismatch repair gene hMSH6 have been identified in a subset of tumors with low-frequency microsatellite instability. In addition to epithelial tumors of the colon, endometrium, and ovary, microsatellite instability has been reported to occur also in sporadic melanoma. The relationship between microsatellite instability and mismatch repair in melanoma cells, however, has not been investigated so far. In this study, we analyzed microsatellite instability, mismatch repair activity, and expression of the hMSH2, hMSH6, hMLH1, and hPMS2 proteins in five melanoma cell lines and in tumor specimens from which the cells were derived. Four cell lines displayed normal levels of mismatch repair activity and expressed all the mismatch repair proteins. The extracts of the fifth cell line lacked the hMLH1 and hPMS2 proteins, and were correspondingly deficient in the repair of DNA mismatches. This line displayed high-frequency microsatellite instability, whereas the four mismatch-repair-proficient cell lines displayed either no or low-frequency microsatellite instability. These findings could be confirmed in the tumor specimens, in that only the tumor that did not express hMLH1 and hPMS2 displayed high-frequency microsatellite instability. Our data are consistent with the hypothesis that in melanoma, similarly to epithelial tumors, only the high-frequency microsatellite instability phenotype is strictly dependent on a defective mismatch repair system. Further studies on a large series of tumor specimens are required to establish the frequency of mismatch repair loss in human melanoma.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research|
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Deposited On:||09 Jul 2010 16:20|
|Last Modified:||29 Nov 2013 21:49|
|Publisher:||Nature Publishing Group|
|Free access at:||Publisher DOI. An embargo period may apply.|
|Citations:||Web of Science®. Times cited: 25|
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